Process for the synthesis of cleistanthin

Abstract

The present invention relates to a process for preparing compound of formula (I) that is Cleistanthin A. The process comprises the steps of reacting compound of formula (II) with compound of formula (III) in the presence of a first solvent, quarternary ammonium salt and first alkali to form compound of formula (IV). The compound of formula (IV) is further treated with a second solvent and a second alkali to form compound of formula (I). The present invention also relates to the preparation of salt of compound of formula (IV) that is Cleistanthin A acetate.

1 . A process for preparing compound of formula I, wherein the process comprises the steps of:
 reacting compound of formula II with compound of formula III in the presence of a first solvent, quarternary ammonium salt and first alkali to form compound of formula IV;   treating compound of formula IV with a second alkali and a second solvent to form compound of formula I.   
       
         
           
           
               
               
           
         
       
     
     
         2 . The process as claimed in  claim 1  wherein the first solvent is dichloromethane. 
     
     
         3 . The process as claimed in  claim 1  wherein the first alkali is sodium hydroxide. 
     
     
         4 . The process as claimed in  claim 1  wherein the quarternary ammonium salt is tetrabutyl ammonium bromide. 
     
     
         5 . The process as claimed in  claim 1  wherein the second alkali is potassium carbonate. 
     
     
         6 . The process as claimed in  claim 1  wherein the second solvent is methanol. 
     
     
         7 . A process for preparing compound of formula IV, wherein the process comprises the steps of:
 reacting compound of formula II with compound of formula III in the presence of a solvent, quarternary ammonium salt and alkali to form compound of formula IV.   
       
         
           
           
               
               
           
         
       
     
     
         8 . The process as claimed in  claim 7  wherein the solvent is dichloromethane. 
     
     
         9 . The process as claimed in  claim 7  wherein the alkali is sodium hydroxide. 
     
     
         10 . The process as claimed in  claim 7  wherein the quarternary ammonium salt is tetrabutyl ammonium bromide. 
     
     
         11 . The process as claimed in  claim 1 , wherein the compound of formula II is prepared by reducing compound of formula IX in the presence of lithium aluminium hydride and tetrahydrofuran. 
       
         
           
           
               
               
           
         
       
     
     
         12 . The process as claimed in  claim 11 , wherein the compound of formula IX is prepared by reacting compound of formula VIII with diethyl acetylenedicarboxylate in the presence of acetic acid and methylene dichloride. 
       
         
           
           
               
               
           
         
       
     
     
         13 . The process as claimed in  claim 12 , wherein the compound of formula VIII is prepared by treating compound of formula VII with n-butyl lithium in the presence of tetrahydrofuran and piperonal. 
       
         
           
           
               
               
           
         
       
     
     
         14 . The process as claimed in  claim 13 , wherein the compound of formula VII is prepared by treating compound of formula VI with p-ethylene glycol in the presence of p-toluene sulphonic acid. 
       
         
           
           
               
               
           
         
       
     
     
         15 . The process as claimed in  claim 14 , wherein the compound of formula VI is prepared by treating compound of formula V with bromine in the presence of acetic acid. 
       
         
           
           
               
               
           
         
       
     
     
         16 . The process as claimed in  claim 1 , wherein the compound of formula III is prepared by reacting compound of formula XV with HBr in acetic acid in the presence of dichloromethane. 
       
         
           
           
               
               
           
         
       
     
     
         17 . The process as claimed in  claim 16 , wherein the compound of formula XV is prepared by treating compound of formula XIV with acetic acid in the presence of acetic anhydride and pyridine. 
       
         
           
           
               
               
           
         
       
     
     
         18 . The process as claimed in  claim 17 , wherein the compound of formula XIV is prepared by treating compound of formula XIII with methanol and sodium methoxide to form a residue, which is further treated with dimethyl formamide in the presence of sodium hydride and methyl iodide. 
       
         
           
           
               
               
           
         
       
     
     
         19 . The process as claimed in  claim 18 , wherein the compound of formula XIII is prepared by treating compound of formula XII with 2,6lutidine, tetrabutyl ammonium bromide, anhydrous dichloromethane and ethanol. 
       
         
           
           
               
               
           
         
       
     
     
         20 . The process as claimed in  claim 19 , wherein the compound of formula XII is prepared by treating compound of formula XI with HBr in acetic acid in the presence of dichloromethane. 
       
         
           
           
               
               
           
         
       
     
     
         21 . The process as claimed in  claim 20 , wherein the compound of formula XI is prepared by reacting compound of formula X with acetic anhydride in the presence of pyridine.